Method of preparing brominated hydroxy aromatic compounds

ABSTRACT

Direct bromination of hydroxy aromatic compounds by electrolysis of mixtures comprising the hydroxy aromatic compound, a source of bromide ion, and an organic solvent provides product brominated hydroxy aromatic compounds at synthetically useful rates with high para-selectivity. The process does not require the use or handling of molecular bromine or bromine complexes and allows the full use of the bromide source without generating hydrogen bromide as a by-product of the reaction. The simple electrochemical equipment required by the present process, for example an undivided electrochemical cell, makes the process less capital intensive than analogous electrochemical processes carried out in divided cells. The use of hydrobromic acid as the source of bromide ion provides clean reaction with nearly exclusive formation of the target brominated product.

BACKGROUND OF THE INVENTION

[0001] This invention relates to an electrochemical method for thebromination of hydroxy aromatic compounds. More particularly the presentinvention provides a method for the preparation of brominated phenolssuch as para- bromophenol.

[0002] Brominated hydroxy aromatic compounds such as para- bromophenolare valuable intermediates for production of bisphenols such as4,4′-biphenol and hydroquinone. 4,4′-biphenol may be prepared bycoupling para- bromophenol, and hydroquinone may be prepared byhydrolysis of para-bromophenol. In addition, brominated phenols areversatile intermediates in the preparation of organic dyestuffs, and assynthons for agricultural chemicals used for plant protection. It isknown that molecular bromine, Br₂, reacts readily with phenol to formpredominantly bromophenol. However, although the reaction rate is high,the selectivity of the reaction is relatively poor, para/orthoselectivity of only about 75% being typical. In addition, significantamounts of the “over-brominated” product, 2,4-dibromophenol, are formed.It should be noted as well that the use and handling of molecularbromine, a volatile, toxic liquid at room temperature, poses significantengineering challenges to prevent its adventitious release into theenvironment, as well as human health concerns related to the acutetoxicity of molecular bromine.

[0003] Various attempts have been made to improve selectivity in thebromination of phenol with molecular bromine, and in some aspects theseefforts have been successful. Thus, the use of tetraalkylammonium saltsof the Br₃ ⁻anion afforded improved selectivity during the brominationof phenol. However, the improved selectivity came at the expense of lowreaction rates. Moreover, the tetraalkylammonium bromides are costly andmust be recovered and recycled. Other salts of the tribromide anion (Br₃⁻) have also been used for bromination reactions of phenol. Complexes ofmolecular bromine with alkylsulfides have demonstrated good selectivityfor para-bromination of phenol but possess many of the samedisadvantages as the organic salts of tribromide anion. Other schemes toimprove selectivity in bromination reactions of phenol have employedcombinations of molecular bromine with silica, and molecular bromine andcyclodextrin. Here again, however, selectivity was insufficient.Moreover, bromination reactions based upon molecular bromine or itscomplexes use only half of the bromine introduced and produce a fullequivalent of hydrogen bromide, HBr, as a by-product. To date, thehighest selectivity observed in the bromination of phenol was achievedby reaction of phenol with a brominating agent based upon a combinationof HBr, molecular oxygen, and a heteropolyacid catalyst. Despite thehigh selectivity observed (99%) in the bromination of phenol, theprocess suffers from low catalyst turnover, the high molecular weight ofthe catalyst, and the high cost of the catalyst.

[0004] Some years ago, it was reported that the electrolysis of aqueoussolutions of phenol in the presence of a bromide salt as the electrolyteafforded predominantly para-bromophenol (T.Bejerano, E.Gileadi,Electrochimica Acta, 1976, vol. 21, p. 231). The method disclosed onlyvery low concentrations of reactants suggesting that such a method wasunlikely to be useful for the preparation of substantial amounts ofbromophenol product. Moreover, the low para/ortho selectivity observedcast doubt upon the method's viability in as a modern industrialpractice.

[0005] It is clear from the foregoing discussion that new processeswhich are not dependent upon the use of molecular bromine for thepreparation of brominated hydroxy aromatic compounds such as bromophenolrepresent very attractive goals, especially if the new processes areboth highly selective and efficient. The present invention provides anew, highly selective and highly efficient electrochemical method forthe preparation of brominated hydroxy aromatic compounds. The new methoddoes not require the use of molecular bromine.

BRIEF SUMMARY OF THE INVENTION

[0006] In one aspect the present invention relates to a method for thepreparation of brominated hydroxy aromatic compounds, said methodcomprising: electrolyzing in an electrochemical cell a mixturecomprising a hydroxy aromatic compound, at least one source of bromideion, at least one organic solvent, and optionally water, to provide aproduct brominated hydroxy aromatic compound.

[0007] In another aspect the present invention provides anelectrochemical method for the preparation of bromophenols such as para-bromophenol and 4-bromo-2-methylphenol. In yet another aspect the methodof the present invention comprises recovering the product brominatedhydroxy aromatic compound from a product mixture.

DETAILED DESCRIPTION OF THE INVENTION

[0008] The present invention may be understood more readily by referenceto the following detailed description of preferred embodiments of theinvention and the examples included therein. In the followingspecification and the claims which follow, reference will be made to anumber of terms which shall be defined to have the following meanings:

[0009] The singular forms “a”, “an” and “the” include plural referentsunless the context clearly dictates otherwise.

[0010] “Optional” or “optionally” means that the subsequently describedevent or circumstance may or may not occur, and that the descriptionincludes instances where the event occurs and instances where it doesnot.

[0011] As used herein the term “aliphatic radical” refers to a radicalhaving a valence of at least one comprising a linear or branched arrayof atoms which is not cyclic. The array may include heteroatoms such asnitrogen, sulfur and oxygen or may be composed exclusively of carbon andhydrogen. Examples of aliphatic radicals include methyl, methylene,ethyl, ethylene, hexyl, hexamethylene and the like.

[0012] As used herein the term “aromatic radical” refers to a radicalhaving a valence of at least one comprising at least one aromatic group.Examples of aromatic radicals include phenyl, pyridyl, furanyl, thienyl,naphthyl, phenylene, and biphenyl. The term includes groups containingboth aromatic and aliphatic components, for example a benzyl group.

[0013] As used herein the term “cycloaliphatic radical” refers to aradical having a valance of at least one comprising an array of atomswhich is cyclic but which is not aromatic. The array may includeheteroatoms such as nitrogen, sulfur and oxygen or may be composedexclusively of carbon and hydrogen. Examples of cycloaliphatic radicalsinclude cyclopropyl, cyclopentyl cyclohexyl, tetrahydrofuranyl and thelike.

[0014] As used herein the term “over-bromination” refers to thesubstitution of more than one hydrogen atom in a hydroxy aromaticcompound by bromine atoms. Over-bromination is illustrated by thetransformation of phenol into 2,4-dibromophenol which entails thesubstitution of two hydrogen atoms in the starting hydroxy aromaticcompound, phenol, by bromine atoms.

[0015] As used herein the term “hydrobromic acid” is interchangeablewith the term “aqueous hydrogen bromide” and means a mixture of hydrogenbromide (HBr) and water.

[0016] It has been discovered that electrolysis of relativelyconcentrated mixtures comprising a hydroxy aromatic compound, a sourceof bromide ion, and an organic solvent results in relatively efficientbromination of the hydroxy aromatic compound. For example, it was foundthat when a mixture of phenol, hydrobromic acid, and acetonitrile wassubjected to electrolysis in an electrochemical cell, the productproduced was predominantly p-bromophenol. Overall, the process isillustrated by the phenol to para-bromophenol transformation representedby equation (1).

C₆H₅OH+Hr→BrC₆H₄OH+H₂  (1)

[0017] Electrosynthesis of brominated hydroxy aromatic compoundsaccording to the method of the present invention may be carried outconveniently in an electrochemical cell. The electrochemical cell may beeither a divided or an undivided cell. Frequently the use of anundivided electrochemical is preferred since sufficiently high currentefficiencies (>95%) may be achieved in undivided cells when usedaccording to the method of the present invention. The electrochemicalcells may comprise almost any type of electrodes although the use ofgraphite electrodes is preferred. In one embodiment of the presentinvention the anode of the electrochemical cell employed consists of agraphite electrode, and the cathode consists of another suitablematerial which is not graphite. Typically, the electrochemical cell usedaccording to the method of the present invention is operated at acurrent density in a range between about 20 and about 1000 milliamperesper square centimeter (mA/cm²), preferably between about 50 and about400 mA/cm 2, and even more preferably between about 100 and about 250mA/cm². Typically, the cell is operated at a cell voltage higher thanabout 1.5 volts (V), preferentially in a range between about 3 and about4 V.

[0018] As mentioned, the method of the present invention compriseselectrolyzing in an electrochemical cell a mixture comprising a hydroxyaromatic compound, at least one source of bromide ion, and at least oneorganic solvent. Typically the hydroxy aromatic compound is used in anamount corresponding to greater than 5 percent of the entire weight ofthe mixture undergoing electrolysis. In one embodiment the hydroxyaromatic compound is used in an amount corresponding to between 5percent and about 50 percent of the entire weight of the mixtureundergoing electrolysis. Under such circumstances, the concentration ofthe hydroxy aromatic compound is defined as being between 5 and about 50percent by weight of the mixture. In an alternate embodiment the hydroxyaromatic compound is used in an amount corresponding to between about 10percent and about 40 percent of the entire weight of the mixtureundergoing electrolysis. Suitable hydroxy aromatic compounds which maybe used according to the method of the present invention includemonofunctional phenols having structure I

[0019] wherein R¹ is independently at each occurrence a halogen atom, aC₁-C₂₀ aliphatic radical, a C₄-C₂₀ aromatic radical, or a C₃-C₂₀cycloaliphatic radical, and n is an integer having a value of from 0 to4.

[0020] Monofunctional phenols having structure I are illustrated byphenol, ortho-cresol (2-methylphenol), 2-chlorophenol,2-tert-butylphenol, 2-phenylphenol, 2-isopropyl-5-methylphenol, and thelike.

[0021] In addition to monofunctional phenols having structure I,suitable hydroxy aromatic compounds which may be used according to themethod of the present invention include hydroxynaphthalenes havingstructure II

[0022] wherein R² and R³ are independently at each occurrence a halogenatom, C₁-C₂₀ aliphatic radical, a C₄-C₂₀ aromatic radical, or a C₃-C₂₀cycloaliphatic radical, m is an integer from 0 to 2, and p is an integerfrom 0 to 4.

[0023] Hydroxynaphthalenes having structure II are illustrated by1-naphthol, 2-naphthol, 2-methyl-1-naphthol, 2-chloro-1-naphthol,2-tert-butyl-1-naphthol, and the like.

[0024] The source of bromide ion used according to the method of thepresent invention may be any bromine containing compound which furnishesionic bromide ion under the conditions present in the electrochemicalcell. Thus, suitable sources of bromide ion include hydrobromic acid,alkali metal bromides, transition metal bromides, quaternary ammoniumbromides, amine hydrobromides, quaternary phosphonium bromides, and thelike. In one embodiment of the present invention the source of bromideion is a solution of 48 percent by weight hydrobromic acid in water. Inan alternate embodiment the source of bromide ion is a mixture of sodiumbromide and hydrobromic acid. Many different combinations of bromide ionsources may be used advantageously according to the method of thepresent invention. In some embodiments at least one transition metalbromide in addition to a non-transition metal bromide source such ashydrobromic acid is present in the reaction mixture undergoingelectrolysis. In another embodiment, at least one quaternary ammoniumbromide or quaternary phosphonium bromide in addition to a bromidesource such as hydrobromic acid which is neither a quaternary ammoniumor quaternary phosphonium bromide is present in the reaction mixtureundergoing electrolysis. Regardless of the source of the bromide ion, ithas been found that in instances in which the molar ratio of the hydroxyaromatic compound to bromide ion from any source is less than about 1the reaction shows greater selectivity for monobromination and“over-bromination” is avoided.

[0025] Transition metal bromides which may be advantageously employedaccording to the method of the present invention include CuBr₂, FeBr₂,ZnBr₂, and CoBr₂. In some instances it may be advantageous to employmixtures of transition metal bromides. Quaternary ammonium bromides areillustrated by tetrabutylammonium bromide, tetraethylammonium bromide,tetramethylammonium bromide, and the like. Amine hydrobromides areillustrated by triethylamine hydrobromide, diethylamine hydrobromide,trimethylamine hydrobromide, ammonium bromide, and the like. Quaternaryphosphonium bromides are illustrated by tetrbutylphosphonium bromide,tetramethylphosphonium bromide, and the like.

[0026] In some embodiments the source of bromide ion employed compriseshydrobromic acid generated by combining an acid with an alkali metalbromide, for example a combination of sodium bromide and aqueoussulfuric acid. The combination of sodium bromide and aqueous sulfuricacid is shown herein to be suitable source of bromide ion for useaccording to the method of the present invention.

[0027] Organic solvents suitable for use according to the method of thepresent invention include nitrites, esters, alcohols, esters, amides,ketones, and ethers. Typically nitrites such as acetonitrile arepreferred. Suitable solvents include acetonitrile, propionitrile,tetrahydrofuran, N,N-dimethylformamide, 1-methyl-2-pyrrolidinone,diglyme, tetraglyme, ethanol, and methanol. In some instances theorganic solvent employed may affect the selectivity of the brominationreaction.

[0028] In embodiments in which the mixture being electrolyzed containswater, as when, for example, the source of bromide ion compriseshydrobromic acid, the choice of solvent made may affect the homogeneityor heterogeneity of the mixture. Thus the mixture undergoingelectrolysis according to the method of the present invention may be asingle phase system or a multiphase system. An example of a multiphasesystem is a mixture of phenol, aqueous HBr, and propionitrile. Anexample of a single phase system is a mixture of phenol, aqueous HBr,sodium bromide, and methanol.

[0029] The method of the present invention may be practiced as acontinuous process or a batch-type process. In continuous embodiments ofthe present invention the electrochemical cell employed is comprisedwithin a flow reactor. Thus a mixture comprising a hydroxy aromaticcompound, a source of bromide ion, and an organic solvent arecontinuously introduced into a flow reactor comprising at least oneelectrochemical cell, and an effluent stream containing productbrominated hydroxy aromatic compound is continuously removed from theflow reactor. The flow reactor may simply be the electrochemical cellitself, or two or more electrochemical cells arranged in series, or twoor electrochemical cells arranged in parallel, or three or moreelectrochemical cells arrayed in a network arrangement. A networkarrangement of electrochemical cells comprises cells arrayed in at leastone parallel arrangement, and at least one series arrangement. In oneembodiment, the electrochemical cell (or cells) is a bipolarelectrochemical cell. In an alternate embodiment the flow reactorcomprises a series of stirred tank reactors each of said stirred tankreactors comprising an electrochemical cell. Typically, it is preferredthat the flow reactor consist of one or more “flow” electrochemicalcells. In yet another embodiment the product brominated hydroxy aromaticcompound is continuously isolated by precipitation into water andfiltration on a continuous rotary filtration device such as a Bird-Youngrotary vacuum filter.

[0030] In embodiments of the present invention which are batch-typeprocesses the electrochemical cell is comprised within a batch reactor.The batch reactor may be the electrochemical cell itself oralternatively the electrochemical cell may be a component of the batchreactor, for example as where the electrochemical cell is containedwithin a circulating loop of a stirred tank reactor. In one embodimentthe electrochemical cell is a bipolar electrochemical cell. As in thecontinuous embodiments, the product brominated hydroxy aromatic compoundmay be isolated by dilution into water followed by filtration.Alternatively, the product may be isolated by standard methods such asdilution with a water immiscible solvent, washing the resultant organicphase with water, drying and evaporating to afford a crude brominatedhydroxyaromatic compound which is then purified at need bycrystallization, distillation, or like method.

[0031] The product brominated hydroxy aromatic compound may be abrominated phenol having structure m

[0032] wherein R¹ and n are defined as in structure I.

[0033] Brominated hydroxy aromatic compounds having structure III areexemplified by 4-bromo-2-chlorophenol, 4-bromo-2-methyphenol,4-bromo-2-tert-butylphenol, and para-bromophenol.

[0034] Alternatively the product brominated hydroxy aromatic compoundmay be a bromonaphthol having structure IV

[0035] wherein R², R³, m, and p are defined as in structure II.

[0036] Bromonaphthols having structure IV are exemplified by4-bromo-1-naphthol, 4-bromo-2-chloro-1-naphthol,4-bromo-2-methyl-1-naphthol, and 4-bromo-2-tert-butyl-1-naphthol.

[0037] In one embodiment the present invention provides a method for thepreparation of a brominated hydroxy aromatic compound having structureIII, said method comprising:

[0038] (A) electrolyzing in an electrochemical cell a mixture comprisinga hydroxy aromatic compound having structure I, aqueous hydrogenbromide, and at least one organic solvent; and

[0039] (B) recovering the product brominated hydroxy aromatic compound.

[0040] In another embodiment the present invention provides a method forthe preparation of para-bromophenol, said method comprising:

[0041] (A) electrolyzing in an electrochemical cell a mixture comprisingphenol, hydrobromic acid, and acetonitrile, said phenol and aqueoushydrogen bromide being present in amounts corresponding to a molar ratioof phenol to hydrogen bromide in a range between about 0.6 to I andabout 1.0 to 1, said electrochemical cell being operated at a currentdensity in a range between about 20 and about 1000 milliamperes persquare centimeter; and

[0042] (B) recovering a product para-bromophenol.

[0043] In yet another embodiment the present invention provides a methodfor the preparation 4-bromo-2-methylphenol, said method comprising:

[0044] (A) electrolyzing in an electrochemical cell a mixture comprisingortho-cresol, hydrobromic acid, and acetonitrile, said ortho-cresol andaqueous hydrogen bromide being present in amounts corresponding to amolar ratio of ortho-cresol to hydrogen bromide in a range between about0.6 to 1 and about 1.0 to 1, said electrochemical cell being operated ata current density in a range between about 20 and about 1000milliamperes per square centimeter; and

[0045] (B) recovering a product 4-bromo-2-methylphenol.

EXAMPLES

[0046] The following examples are set forth to provide those of ordinaryskill in the art with a detailed description of how the methods claimedherein are evaluated, and are not intended to limit the scope of whatthe inventors regard as their invention. Unless indicated otherwise,parts are by weight, temperature is in ° C. Product mixtures wereanalyzed by quantitative HPLC and the percent of starting phenolconverted to product was determined (See “% Phenol Convers.” in Tables1-3). Product selectivities were likewise determined by quantitativeHPLC. Two measurements of product selectivity were made: (i)“para-selectivity” which is defined here as the amount ofpara-bromophenol relative to the total amount of all brominated productspresent in the product mixture, and (ii) “mono-selectivity” which isdefined as the total peak amount of all mono-brominated productsrelative to the total amount of all brominated products present in theproduct mixture. Reaction rates expressed in moles of product per literper hour represent the average reaction rate and are obtained bydividing the number of moles of phenol converted to product by thevolume of the reaction mixture and the reaction time. The column heading“Br/PhOH” in Tables 1-3 is a molar ratio and refers to the total numberof moles of bromide ion from all sources present in the reaction mixturedivided by the number of moles of phenol initially present in thereaction mixture.

Examples 1-14

[0047] Example 1: A glass electrochemical cell equipped with graphiteelectrodes (area 2.5 cm² was charged with 3.544 grams of phenol (PhOH),4.717 grams of hydrobromic acid (48% by weight HBr) and 9.746 gramsacetonitrile (MeCN). Bulk electrolysis was carried out at 3 V constantpotential using a CHI-110 potentiostat over a period of 5.5 hours. Theproduct mixture was analyzed by HPLC.

[0048] Examples 2-14 were carried in a similar fashion using the sameelectrochemical cell but operated at 4 V constant potential. Data forExamples 1-14 are gathered in Table 1. In Example 11 the aqueous HBr wasgenerated from a solution of sodium bromide in aqueous sulfuric acid. InTable 1 the column headings “para %” and “mono %” refer to the“para-selectivity” and “mono-selectivity” measured for each reaction.TABLE 1 ELECTROCHEMICAL BROMINATION OF PHENOL USING HYDROBROMIC ACID ASTHE SOLE BROMIDE SOURCE Rxn % PhOH HBr MeCN Br/ time, Phenol Rate, Paramono Example (grams) (grams) (grams) PhOH hr Convs. mol/Lhr % % 1 2.413.22 8.88 0.75 2 29.6 0.24 90.8 100 2 2.41 4.31 8.35 1.00 2 42.1 0.3488.5 100 3 4.86 6.53 5.37 0.75 2 23.1 0.38 90.1 100 4 4.85 7.61 4.830.88 2 29.2 0.48 90.2 100 5 2.55 4.4 10.05 0.96 3.6 76.3 0.32 89.1 100 62.55 4.24 10.23 0.93 3.6 72.8 0.3 89.6 100 7 3.35 5.65 7.99 0.94 3.637.6 0.22 91.1 100 8 4.11 7.09 5.81 0.96 3.6 47 0.36 90 98.5 9 3 4.59.43 0.84 4 64.4 0.29 88.6 100 10 3.54 4.72 9.75 0.74 6 50.6 0.17 88.2100 11 3.05 3.28 10.78 0.6 6 33.5 0.1 89.4 100 12 3.24 4.44 11.09 0.77 627.3 0.08 93.5 100 13 1.7 2.79 12.5 0.92 7 86.6 0.12 88.9 97.4 14 3.385.86 7.75 0.97 7 63.4 0.19 89.1 96.4

Examples 15-29

[0049] Example 15: A glass electrochemical cell equipped with graphiteelectrodes (area 2.5 cm² was charged with 3.26 grams of phenol, 4.00grams of sodium bromide (NaBr) and 10.4 grams of acetonitrile (MeCN).Bulk electrolysis was carried out at 4 V constant potential over aperiod of 5.5 hours (hr). The product mixture was analyzed by HPLC.

[0050] Examples 16-29 were carried out in a similar fashion using thesame ectrochemical cell operated at 4 V constant potential. Data forExamples 15-29 are gathered in Table 2. In Table 2 the column heading“Br Source” identifies a source of bromide in addition to sodium bromideand aqueous HBr which were used in the reaction. The column heading “WtBr Source” indicates the weight in grams of the additional bromidesource used. Examples 28 and 29 are included in Table 2 as aspace-saving measure. In Examples 28 and 29 no source of bromide inaddition to sodium bromide and HBr was employed. Instead, the reactionmixtures included 0.11 grams of nickel acetate and 0.13 grams of ceriumchloride respectively. TABLE 2 ELECTROCHEMICAL BROMINATION OF PHENOLINCLUDING SODIUM BRMIDE AS THE BROMIDE SOURCE PhOH NaBr HBr Br Wt BrMeCN Example (grams) (grams) (grams) Source Source Solvent (grams) 153.26 4 — — — MeCN 10.4 16 4.17 3.4 1.71 — — MeCN 7.8 17 5.1 3.4 3.4 — —MeCN 5.1 18 8.93 10.02 6.89 — — MeCN 28.2 19 9.72 5.03 5.79 — — MeCN31.6 20 5.68 0.8 — CuBr2 0.2 tetraglyme 9.9 21 4.68 1.04 — CuBr2 0.12DMF 11.8 22 4.33 1.07 — CuBr2 0.07 DMAA 12.7 23 4.76 1.05 — CuBr2 0.08MeOH 13.1 24 3.82 1.04 3.83 CuBr2 0.06 MeOH 10.6 25 2.79 1.03 1.68 CuBr20.11 MeCN 11.3 26 8.53 5.12 5.8 CuBr2 0.2 MeCN 31.3 27 3.81 1 — FeBr20.17 MeCN 10.8 28 2.93 1.07 1.94 NiOAc2 0.11 MeCN 11.1 29 3.04 1.01 1.31CeCl3 0.13 MeCN 10.6 para- Mono Br/ Voltage Rxn time % Phenol Rate,selectivity selectivity Example PhOH (V) hr Convs. mol/L hr % % 15 0.964 5.5 3.2 0.012 100 100 16 0.97 4 5.5 29.8 0.161 90.4 100 17 0.98 4 5.538.8 0.282 90.4 100 18 1.46 5 5.8 32.8 0.111 92.8 97.1 19 0.81 6 6 33.30.108 91.8 100 20 0.16 2 2 3.3 0.055 100 100 21 0.23 2 6 11 0.047 63.796.4 22 0.24 2 6 10 0.038 83.3 90 23 0.21 4 3.8 13.9 0.087 82.2 96.1 240.82 4 4 16.8 0.087 80.1 92.9 25 0.71 4 1.2 34.5 0.47 93.2 100 26 0.95 43.6 41.7 0.203 92.8 100 27 0.28 4 6 12.4 0.048 100 100 28 0.7 4 3 32.90.188 88.9 100 29 0.54 4 7.5 22.3 0.056 92.5 100

[0051] The electrochemical brominations of Examples 30-38 were out as inExample 15 with the exception that bromide sources other than bromidewere employed. Data for Examples 30-38 are gathered in Table 3. e 3 thecolumn heading “Br Source” identifies bromide sources other than aqueousHBr present in the reaction mixture. The column heading “Wt Br Source”indicates the weight in grams of the bromide source other than aqueousHBr. TABLE 3 ELECTROCHEMICAL BROMINATION OF PHENOL USING ALTERNATEBROMIDE SOURCES Volt- Ex- PhOH HBr Br Wt Br MeCN Br/ age ample (grams)(grams) Source Source (grams) PhOH (V) 30 3.26 2.07 CuBr2 1.19 11.030.66 5 31 3.26 CuBr2 1.19 11.03 0.31 5 32 3.28 1.43 NEt4Br 1.88 9.250.73 4 33 3.3 2 FeBr2 1.01 12.5 0.6 4 34 2.6 1.44 FeBr2 1.18 11.47 0.694 35 2.8 CuBr2 1.31 11.78 0.39 4 36 2.84 1.11 ZnBr2 2.09 13 0.84 5 372.01 LiBr 1.83 13.41 0.84 4 Ex- Rxn time % Phenol Rate, para- mono-ample hr Convs. mol/L hr selectivity % selectivity % 30 6.5 55.1 0.2395.4 97 31 1.9 20.8 0.16 100 100 32 4.3 27.4 0.14 89.4 100 33 2 12.40.11 100 100 34 6 9.8 0.02 100 100 35 4.6 35.5 0.13 96.3 100 36 4.3 33.80.12 90.4 96.4 37 3.5 29.4 0.1 72.6 84.4

Examples 38-41

[0052] Examples 38-41 involved the electrochemical bromination ofortho-cresol (Examples 38-40) and meta-cresol (Example 41). Theelectrochemical brominations of Examples 38-41 were carried out in amanner analogous to the procedure used in Example 1. Results aregathered in Table 4. As in Table 1, the column headings “para %” and“mono %” refer to the “para-selectivity” and “mono-selectivity” measuredfor each reaction. The column heading “Br/ ArOH” in Tables 4 is a molarratio and refers to the total number of moles of bromide ion from allsources present in the reaction mixture divided by the number of molesof o-cresol or m-cresol initially present in the reaction mixture. Dataappearing in Table 4 under the column heading “% ArOH Convs.” indicatesthe percentage of o-cresol or m-cresol converted to brominated products.TABLE 4 ELECTROCHEMICAL BROMINATION OF O-CRESOL AND M-CRESOL USINGHYDROBROMIC ACID AS THE SOLE BROMIDE SOURCE Rxn cresol HBr MeCN Br/time, % ArOH Rate, Para mono Example cresol (grams) (grams) (grams) ArOHhr Convs. mol/Lhr % % 38¹ ortho 3.83 5.74 9.60 0.80 4.8 59.2 0.21 98.3100 39² ortho 2.41 4.31 8.35 1.00 2 42.1 0.34 88.5 100 40³ ortho 4.866.53 5.37 0.75 2 23.1 0.38 90.1 100 41² meta 4.85 7.61 4.83 0.88 2 29.20.48 90.2 100

[0053] The data in Tables 1-4 illustrate the versatility of the methodof the present invention. The method is characterized by highselectivity for para bromination and control of unwantedover-bromination is demonstrated by the high values of mono-selectivityobserved. The reaction can be run with a single source of bromide ion,such as aqueous HBr (Examples 1-14 and 38-41). Alternatively, thereaction can be run with multiple sources of bromide ion, for examplemixtures of sodium bromide, aqueous HBr and copper bromide as employedin Examples 24-26. The method of the present invention may even becarried out under anhydrous conditions (See Examples 15 and 20-23)albeit the reaction rates were generally reduced relative to reactionrates observed when aqueous bromide ion was present. Quaternary ammoniumbromides may advantageously be employed as a source of additionalbromide ion (See Example 33). In addition, the data demonstrate thatmethod of the present invention permits the highly selectiveelectrochemical bromination of o-cresol (Examples 38-40) as well asm-cresol (Example 41).

[0054] The invention has been described in detail with particularreference to preferred embodiments thereof, but it will be understood bythose skilled in the art that variations and modifications can beeffected within the spirit and scope of the invention.

What is claimed is:
 1. A method for the preparation of a brominatedhydroxy aromatic compound, said method comprising: electrolyzing in anelectrochemical cell a mixture comprising a hydroxy aromatic compound,at least one source of bromide ion, at least one organic solvent, andoptionally water, to afford a product brominated hydroxy aromaticcompound.
 2. A method according to claim 1 wherein said electrochemicalcell is operated at a current density in a range between about 20 andabout 1000 milliamperes per square centimeter.
 3. A method according toclaim 1 wherein said electrochemical cell comprises a graphite anode. 4.A method according to claim 1 wherein said hydroxy aromatic compound isselected from the group consisting of monofunctional phenols havingstructure I

wherein R1 is independently at each occurrence a halogen atom, a C₁-C₂₀aliphatic radical, a C₄-C₂₀ aromatic radical, or a C₃-C₂₀ cycloaliphaticradical, and n is an integer having a value of from 0 to 4, andhydroxynaphthalenes having structure II

wherein R² and R³ are independently at each occurrence a halogen atom,C₁-C₂₀ aliphatic radical, a C₄-C₂₀ aromatic radical, or a C₃-C₂₀cycloaliphatic radical, m is an integer from 0 to 2, and p is an integerfrom 0 to
 4. 5. A method according to claim 4 wherein said hydroxyaromatic compound is phenol.
 6. A method according to claim 4 whereinsaid hydroxy aromatic compound is ortho-cresol.
 7. A method according toclaim 1 wherein said source of bromide ion comprises hydrobromic acid.8. A method according to claim 7 wherein said source of bromide ionfurther comprises an alkali metal bromide.
 9. A method according toclaim 8 wherein said alkali metal bromide is sodium bromide.
 10. Amethod according to claim 9 wherein said source of bromide furthercomprises at least one transition metal bromide.
 11. A method accordingto claim 10 wherein said transition metal bromide is selected from thegroup consisting of CuBr₂, FeBr₂, ZnBr₂, and CoBr₂.
 12. A methodaccording to claim 7 wherein said source of bromide ion furthercomprises at least one quaternary ammonium bromide.
 13. A methodaccording to claim 1 wherein said source of bromide ion comprises analkali metal bromide.
 14. A method according to claim 13 wherein saidalkali metal bromide is sodium bromide.
 15. A method according to claim1 wherein said organic solvent is selected from the group consisting ofnitriTes, esters, alcohols, esters, amides, ketones, and ethers.
 16. Amethod according to claim 15 wherein said solvent is selected from thegroup consisting of acetonitrile, propionitrile, tetrahydrofuran, N,N-dimethylformamide, 1-methyl-2-pyrrolidinone, diglyme, tetraglyme,ethanol, and methanol.
 17. A method according to claim 1 wherein saidelectrochemical cell is comprised within a flow reactor.
 18. A methodaccording to claim 1 wherein said electrochemical cell is comprisedwithin a batch reactor.
 19. A method according to claim 1 wherein theproduct brominated hydroxy aromatic compound has structure III

wherein R¹ is independently at each occurrence a halogen atom, a C₁-C₂₀aliphatic radical, a C₄-C₂₀ aromatic radical, or a C₃-C₂₀ cycloaliphaticradical, and n is an integer having a value of from 0 to
 4. 20. A methodaccording to claim 19 wherein the product brominated hydroxy aromaticcompound having structure III is selected from the group consisting of4-bromo-2-chlorophenol, 4-bromo-2-methyphenol,4-bromo-2-tert-butylphenol, and para-bromophenol.
 21. A method accordingto claim 1 wherein said product brominated hydroxy aromatic compound isa bromonaphthol having structure IV

wherein R2 and R are independently at each occurrence a halogen atom,C₁-C₂₀ aliphatic radical, a C₄-C₂₀ aromatic radical, or a C₃-C₂₀cycloaliphatic radical, m is an integer from 0 to 2, and p is an integerfrom 0 to
 4. 22. A method according to claim 21 wherein saidbromonaphthol having structure IV is selected from the group consistingof 4-bromo-1-naphthol, 4-bromo-2-chloro-1-naphthol,4-bromo-2-methyl-1-naphthol, and 4-bromo-2-tert-butyl-1-naphthol.
 23. Amethod according to claim 1 wherein the product brominated hydroxyaromatic compound is produced with a para-selectivity of from about 85to about 100 percent.
 24. A method according to claim 1 wherein theproduct brominated hydroxy aromatic compound is produced with amono-selectivity of from about 95 to about 100 percent.
 25. A methodaccording to claim 1 further comprising a product recovery step, saidstep comprising recovering the product brominated hydroxy aromaticcompound from a product mixture.
 26. A method according to claim 25wherein said recovering the product brominated hydroxy aromatic compoundcomprises dilution of a product mixture with water and filtration ofsaid product brominated hydroxy aromatic compound.
 27. A method for thepreparation of a brominated hydroxy aromatic compound having structureIII

wherein R¹ is independently at each occurrence a halogen atom, a C₁-C₂₀aliphatic radical, a C₄-C₂₀ aromatic radical, or a C₃-C₂₀ cycloaliphaticradical, and n is an integer having a value of from 0 to 4, said methodcomprising: (A) electrolyzing in an electrochemical cell a mixturecomprising a hydroxy aromatic compound having structure I

wherein R¹ is independently at each occurrence a halogen atom, a C₁-C₂₀aliphatic radical, a C₄-C₂₀ aromatic radical, or a C₃-C₂₀ cycloaliphaticradical, and n is an integer having a value of from 0 to 4, aqueoushydrogen bromide, and at least one organic solvent; and (B) recoveringthe product brominated hydroxy aromatic compound.
 28. A method accordingto claim 26 wherein said electrochemical cell is operated at a currentdensity in a range between about 20 and about 1000 milliamperes persquare centimeter.
 29. A method for the preparation of para-bromophenol,said method comprising: (A) electrolyzing in an electrochemical cell amixture comprising phenol, hydrobromic acid, and acetonitrile, saidphenol and hydrobromic acid being present in amounts corresponding to amolar ratio of phenol to hydrogen bromide in a range between about 0.6to 1 and about 1.0 to 1, said electrochemical cell being operated at acurrent density in a range between about 20 and about 1000 milliamperesper square centimeter; and (B) recovering a product para-bromophenol.30. A method for the preparation of 4-bromo-2-methylphenol, said methodcomprising: (A) electrolyzing in an electrochemical cell a mixturecomprising ortho-cresol, hydrobromic acid, and acetonitrile, saidortho-cresol and hydrobromic acid being present in amounts correspondingto a molar ratio of ortho-cresol to hydrogen bromide in a range betweenabout 0.6 to 1 and about 1.0 to 1, said electrochemical cell beingoperated at a current density in a range between about 20 and about 1000milliamperes per square centimeter; and (B) recovering a product4-bromo-2-methylphenol.